title: Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents.
abstract: In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1-6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole] was the most active of the series, showing an IC(50) of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC(50) = 22.2 μM). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1-6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC(50) value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC(50) = 28.5 μM).
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México. cdr.romero@live.com.mx
authors.forename: Aurelio
authors.initials: A
authors.lastname: Romero-Castro
authors.forename: Ismael
authors.initials: I
authors.lastname: León-Rivera
authors.forename: Laura Citlalli
authors.initials: LC
authors.lastname: Avila-Rojas
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nieto-Rodríguez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009578:Nitrobenzenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: C561198:2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole; D000970:Antineoplastic Agents; D001549:Benzamides; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D009578:Nitrobenzenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases